Overexpression of the brain and acute leukemia, cytoplasmic (BAALC) gene is implicated in myeloid leukemogenesis and associated with poor outcome in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. Additionally, high BAALC expression occurs in glioblastoma, melanoma, and childhood gastrointestinal stroma tumors.
Acute myeloid leukemia (AML) is a cytogenetically and molecularly heterogeneous disease. AML is characterized by clonal proliferation of myeloid precursors and maturation arrest of myeloid cells in the bone marrow. Despite cytogenetic- and molecular-based stratification in risk-adapted therapies, 20% to 30% of younger (<60 years) AML patients never achieve a complete remission (CR) and 50% of those who achieve CR later experience disease relapse. Older AML patients fare much worse with a two-year median overall survival (OS) of approximately 6%. These numbers show that despite recent advances in understanding AML pathogenesis, overall prognosis remains poor.
Conventional approaches to treating cancer, including hematologic malignancies, and to predicting and assessing cancer and cancer cell responses to specific treatment regimens rely on properly classifying the type of tumor present. Proper classification, in turn, relies primarily on clinical features, tumor cell morphology, tumor cell immunophenotype and, to a lesser extent, on tumor cell chromosomal abnormalities. However, even within a given tumor type, response to specific treatment regimens can be variable, and analyses at the molecular level reveal that the tumor types defined by conventional classification schemes are, often, quite heterogeneous.
Recent efforts to classify tumors, including hematologic malignancies, have, therefore, focused on identifying the specific genetic abnormalities or molecular triggers that drive the growth or pathology of specific tumor types. Such genetic abnormalities or molecular triggers can then serve as markers of disease and/or as targets for therapy.
Tumor protein 53, (also known as tp53, p53, and protein 53), is a tumor suppressor protein that is encoded by the TP53 gene. It is important in cancer suppression, and plays a role in apoptosis, genomic stability, and inhibition of angiogenesis.
It would be desirable and advantageous to have one or a combination of biomarkers which could be used to determine a subject's risk of disease, response to an agent, or the suitability of a subject to treatment with one or more agents using various doses and dose regimens.
In addition, there is a need in the art for methods of downregulating the expression of genes associated with tumorigenesis or cell transformation to treat or prevent cancer. It would be desirable to have additional therapeutic compounds for treating leukemia and other cancers.